Paraventricular nucleus CRH neurons encode stress controllability and regulate defensive behavior selection

Daviu, Núria; Füzesi, Tamás; Rosenegger, David; Rasiah, Neilen P.; Sterley, Toni-Lee; Peringod, Govind; Bains, Jaideep S.

doi:10.1038/s41593-020-0591-0

Cited by 137 publications

(139 citation statements)

References 42 publications

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“…Social buffering of stress-induced grooming behavior and STP CRH PVN neurons play a crucial role in multiple stress-related behaviors (Füzesi et al, 2016;Zhang et al, 2017;Sterley et al, 2018;Daviu et al, 2020). Immediately after an acute stress, CRH PVN neurons, through collateral projections to the lateral hypothalamus, drive self-grooming (Füzesi et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

Sex-specific vasopressin signaling buffers stress-dependent synaptic changes in female mice

Loewen

Baimoukhametova

Bains

2020

Preprint

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In many species, social networks provide benefit for both the individual and the collective. In addition to transmitting information to others, social networks provide an emotional buffer for distressed individuals. Our understanding about the cellular mechanisms that contribute to buffering is poor. Stress has consequences for the entire organism, including a robust change in synaptic plasticity at glutamate synapses onto corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN). In females, however, this stress-induced metaplasticity is buffered by the presence of a naïve partner. This buffering may be due to discrete behavioral interactions, signals in the context in which the interaction occurs (i.e. olfactory cues), or it may be influenced by local signaling events in the PVN. Here, we show that local vasopressin (VP) signaling in PVN buffers the short-term potentiation (STP) at glutamate synapses after stress. This social buffering of metaplasticity, which requires the presence of another individual, was prevented by pharmacological inhibition of the VP 1a receptor in female mice. Exogenous VP mimicked the effects of social buffering and reduced STP in CRH PVN neurons from females but not males. These findings implicate VP as a potential mediator of social buffering in female mice. Significance StatementIn many organisms, including rodents and humans, social groups are beneficial to overall health and well-being. Moreover, it is through these social interactions that the harmful effects of stress can be mitigated-a phenomenon known as social buffering. In the present study, we describe a critical role for the neuropeptide vasopressin in social buffering of synaptic metaplasticity in stress-responsive corticotropin-releasing hormone neurons in female mice. These effects of vasopressin do not extend to social buffering of stress behaviors, suggesting this is a very precise and local form of sex-specific neuropeptide signaling.

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Section: Resultsmentioning

confidence: 99%

Sex-specific vasopressin signaling buffers stress-dependent synaptic changes in female mice

Loewen

Baimoukhametova

Bains

2020

Preprint

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“…Once active, these neurons initiate the production of CORT via the HPA axis, which is an essential component of an appropriate stress response. Recent observations show these neurons have functions beyond endocrine control 2,24,41,42 . Since these neurons have important roles in many different outputs, a mechanism of escaping persisting feedback may be an adaptive means of maintaining their influence over their various functions.…”

Section: Discussionmentioning

confidence: 99%

“…Fiber photometry has emerged as a relatively accessible technique for interrogating neuronal population activity by measuring GCaMP fluorescence 22,23 . We have previously shown that in vivo fiber photometry with GCaMP6s works reliably in CRH PVN neurons 24 . Here we first conducted a series of experiments to validate the quantification of GCaMP6s transients as a measure of neural activity, and assessed signal stability for repeated recordings.…”

Section: Validation Of Fiber Photometry For Repeated Recordings In Vivomentioning

confidence: 99%

Adaptive synaptic plasticity maintains CRH neuron output during chronic glucocorticoid exposure

Rasiah

Rosenegger

Abant

et al. 2020

Preprint

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An increase in circulating glucocorticoids (CORT) is an essential part of the response to stress. Sustained elevations of CORT, however, have dramatic consequences on behavior, endocrine systems and peripheral organs. Critically, they dampen the endocrine response to acute challenges and decrease intrinsic excitability of corticotropin-releasing hormone neurons in the paraventricular nucleus (CRH PVN ), suggesting key circuits may be less responsive to stress. Here, we make the surprising discovery that CRH PVN neurons harness a form of adaptive synaptic scaling to escape the persistent negative feedback pressure from CORT and maintain stable output in vivo. Specifically, there is an increase in glutamatergic drive to these cells that is mediated by a postsynaptic, multiplicative increase in synaptic strength. These findings suggest that dysfunctions associated with chronic stress may not be due to the primary actions of CORT, but instead reflect the emergence of synaptic adaptations as networks seek to re-establish intrinsic activity setpoints.

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“…Inhibition in the PVN during non-stress states CRH PVN neurons gate the endocrine and behavioural stress response. Activity in these cells drive the release of corticosteroids 19 and the manifestation of stress-related behaviours [19][20][21] . To prevent these responses at inappropriate times, the PVN receives robust inhibitory inputs, compromising approximately 50% of all synaptic input 47 , that largely function to curtail CRH PVN neuron activity 9,48 .…”

Section: Discussionmentioning

confidence: 99%

“…Corticotropin-releasing hormone neurons of the paraventricular nucleus of the hypothalamus (CRH PVN ) gate the hormonal 19 and behavioural [19][20][21] responses to stress. In the absence of stress, the activity of CRH PVN neurons is curtailed by robust inhibitory tone.…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal chloride dynamics in hypothalamic CRH^PVNneurons

Lanz

Gordon

Bains

2020

Preprint

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Chloride (Cl -) dynamics shape inhibitory neurotransmission in the brain. In the hypothalamus, GABA signalling onto corticotropin-releasing hormone (CRH PVN ) neurons can switch from inhibitory to excitatory during stress. Although Clfluctuations mediate this stress-dependent shift in GABA signalling, the underlying Cldynamics are poorly understood. Here, using a novel optogenetic strategy to load intracellular Clusing halorhodopsin, we demonstrate that KCC2 rapidly restores Clsetpoints in CRH PVN neurons from naïve animals, but that this process is slowed following stress. Further, we report that somatic Clhomeostasis remains intact after stress. Our results strongly support the idea that KCC2 functions primarily to maintain Clsetpoints and that inhibitory synapses onto dendritic and somatic compartments of CRH PVN neurons are differentially regulated during stress.

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Paraventricular nucleus CRH neurons encode stress controllability and regulate defensive behavior selection

Cited by 137 publications

References 42 publications

Sex-specific vasopressin signaling buffers stress-dependent synaptic changes in female mice

Sex-specific vasopressin signaling buffers stress-dependent synaptic changes in female mice

Adaptive synaptic plasticity maintains CRH neuron output during chronic glucocorticoid exposure

Spatiotemporal chloride dynamics in hypothalamic CRH^PVNneurons

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Paraventricular nucleus CRH neurons encode stress controllability and regulate defensive behavior selection

Cited by 137 publications

References 42 publications

Sex-specific vasopressin signaling buffers stress-dependent synaptic changes in female mice

Sex-specific vasopressin signaling buffers stress-dependent synaptic changes in female mice

Adaptive synaptic plasticity maintains CRH neuron output during chronic glucocorticoid exposure

Spatiotemporal chloride dynamics in hypothalamic CRHPVNneurons

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Spatiotemporal chloride dynamics in hypothalamic CRH^PVNneurons